1. Field of the Invention
The field of the present invention is methods relating to the analysis of alveolar breath as it is expired.
2. Background
Most human adults have a lung capacity of approximately 5-6 liters. Of this capacity, approximately only 0.3 liters is involved with the exchange of gases between blood and breath which takes place in the alveoli. Within this 0.3 liters, called the alveolar breath, oxygen and nitrogen dioxide rapidly diffuse across the epithelial membrane separating blood from breath due to concentration gradients existing between the blood and breath. As a result, the concentration of many gaseous constituents in the alveolar breath closely reflect the partial pressure of the same constituents in blood.
Also present in alveolar breath are trace concentrations of molecules that are small enough to diffuse through the epithelial membrane. Some of these molecules have been shown to be indicative of disorders such as diabetes, lung cancer, and renal failure. Furthermore, depending on the severity of the disorder, such molecules may be present in alveolar breath in the parts per billion range (ppb) or in the parts per trillion range (ppt). Measurement of these trace components is therefore desirable for the early diagnosis of these disorders.
Measuring the concentration of these trace components in alveolar breath as the breath is expired requires determining when alveolar breath is present and being able to detect extremely minute amounts of the trace component. During respiration, of the six liter total lung capacity, only 0.5 liters (called the tidal volume) is exchanged with the ambient atmosphere. However, this 0.5 liters is not the only constituent of a normally expired breath. The first part of expired breath consists essentially of air from the mouth, nose, and upper respiratory tract. The next part of expired breath consists essentially of air from the bronchi and lower respiratory tract. Neither of these first two parts of expired breath includes gases that are exchanged with blood. Therefore, the concentration of a particular gas in either of these two parts does not necessarily reflect the partial pressure of that gas in the blood. The third and last part of expired breath consists essentially of alveolar breath. Alveolar breath is included in the 0.5 liters of tidal volume and contains gases that are exchanged with blood. Thus, the concentration of a gaseous component in alveolar breath closely reflects the partial pressure of that component in the blood.
Methods that are commonly employed to ensure that concentration measurements are being taken only from alveolar breath when it is expired are disclosed in U.S. Pat. No. 5,971,937 to Ekström. In general, Ekström discloses a method and device for measuring the concentrations of alcohol and carbon dioxide on expired breath using infrared spectrometry. In Ekström, the concentrations of alcohol and carbon dioxide in expired breath are periodically measured during expiration. Differences in the method disclosed in Ekström arise in determining when alveolar breath is present. When alveolar breath is determined to be present, the concentration measurements taken for alcohol are accepted as measurements that reflect the partial pressure of alcohol in the blood. All other alcohol concentration measurements are discarded as not reflecting blood alcohol levels.
A first method disclosed in Ekström relies on the volume of breath expired to identify the alveolar breath component of the expired breath. This method assumes that after a certain volume of breath has been expired, alveolar breath is subsequently expired and available for analysis. Breath volume, however, is not a reliable indicator of alveolar breath because breathing patterns and lung capacities vary between individuals. Additionally, the breathing pattern of a single individual may easily vary from breath to breath. Thus, because breath volume can vary so widely, it cannot be reliably used to identify alveolar breath during expiration.
A second method disclosed in Ekström relies on a predetermined amount of time passing before taking measurements of what is presumed to be alveolar breath. However, time is also not reliable to identify alveolar breath during expiration for the same reasons that volume is not reliable. Due to wide variations in breathing patterns, the expiration of alveolar breath cannot be accurately determined based upon the assumption that alveolar breath is expired after an individual exhales for a certain period of time.
A third method disclosed in Ekström is intended to eliminate false positive and false negative measurements of breath alcohol concentrations. Briefly, from the periodic alcohol and/or carbon dioxide concentration measurements, a change, or delta, in the concentrations is calculated between successively measured concentrations of each component. The delta is compared to a predetermined value to locate a plateau in the concentration level(s). The plateau is an indicator of the presence of alveolar breath. Once the plateau is detected, the alcohol concentration measurement taken at or near the time of the last carbon dioxide concentration measurement is accepted as a measurement of the concentration of alcohol in alveolar breath.
In the fourth method disclosed in Ekström, the concentration of carbon dioxide is compared to one or more predetermined values, the values establishing minimum and maximum concentration levels in normally expired breath. The minimum and maximum concentration levels are used to screen out inaccurate alcohol concentration measurements, which might result from hyper- or hypo-ventilation prior to expiring the breath being analyzed. If the carbon dioxide concentration falls within the specified minimum and maximum values, then the alcohol concentration measurement is accepted as an accurate reflection of alcohol in the alveolar breath.
In performing the method disclosed in Ekström, much data are taken that are duplicative or not needed for the concentration determination of alcohol in alveolar breath. For example, if the concentrations of both alcohol and carbon dioxide are monitored to detect the plateau, then one of the concentration measurements is redundant. Additionally, where every carbon dioxide concentration measurement must be compared to the threshold to identify alveolar breath, for those measurements that do not fall within the targeted thresholds, the corresponding alcohol measurements are useless and thus must be discarded.
Thus, an improved method of identifying and analyzing alveolar breath is needed. Such a method should enable alveolar breath to be detected and analyzed in a quick and straightforward manner without taking redundant or useless measurements. The method should also be flexible to accommodate the differences in the breathing patterns among different individuals and the breathing patterns of a single individual over several breaths.